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Value analysis of JAK inhibitors for RA hampered by limited data

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Report, roundtable shed light on critical issues for practicing rheumatologists

The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.

Dr. Christopher Phillips, a community rheumatologist in Paducah, Kentucky, who serves as chair of the insurance subcommittee of the American College of Rheumatology's Committee on Rheumatologic Care

Dr. Christopher Phillips

The direct scope of the review was somewhat limited because it focused primarily on the JAK inhibitor class. While the review does incorporate data supporting the efficacy and safety profile of a biosimilar infliximab product, the review stopped short of digging into a cost-effectiveness analysis of biosimilars. Although the 2017 ICER review found most biologic drugs lacked cost effectiveness at the time, we have seen a more than 20% drop in average sales price for branded and biosimilar infliximab products in the Medicare marketplace since the initial biosimilar approval. Additionally, the review set out to perform comparative effectiveness of the three JAK inhibitors, comparing them with adalimumab, but because of available studies and differences in study design, direct comparison could only be made between upadacitinib and adalimumab, indirect comparison only with tofacitinib, and no comparison with baricitinib. Furthermore, cost-effectiveness analysis was not performed comparing with csDMARDs, which might have been more useful clinically.

ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.

These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.

ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.

Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.

Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.


 

Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.

ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.

Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.

A pricey comparator

In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.

The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.

“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”

Weighing efficacy and cost

Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.

CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).

Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”

After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:

  • Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
  • Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
  • Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.

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